Certain esters of DL- or L-.alpha.-methyl-3,4-di-hydroxyphenylalanine are effective in the treatment of hypertension. The compounds are generally administered in amounts of from about 0.005 to about 300 mg./kg. of body weight of the animal, preferably from about 0.05 to about 100 mg./kg., and especially from about 0.1 to about 25 mg./kg. of body weight of the animal. In this regard, it should be noted that the dosage should be adjusted depending upon the activity of the compound, the response desired in the reduction of blood pressure and also the weight of the animal. For the ranges given above, the more active compounds would tend to be given at the lower dosages and the less active compounds at the higher dosages.
In the preparation of esters of L-.alpha.-methyl-3,4-dihydroxyphenylalanine (also known as L-.alpha.-methyldopa or methyldopa), it is desirable to protect the amino group prior to esterification, otherwise the amino group may participate in the reaction and form undesired products.
It is kown that tert-butoxycarbonyl is an amino blocking group which is easily removed under mild conditions. Typically, the tert-butoxycarbonyl group may be removed by treatment with an acidic reagent such as gaseous hydrogen chloride or trifluoroacetic acid at ambient temperatures in solvents such as benzene or ethyl acetate. Attempts to prepare the N-tert butoxycarbonyl derivative of .alpha.-methyldopa via commonly used reagents such as tert-butoxycarbonyl azide were unsuccessful. It is an object of this invention to provide improved processes for preparing esters of .alpha.-methyl-3,4-dihydroxyphenylalanine having pharmaceutical activity via novel N-(tert-butoxycarbonyl)-intermediates.
Another object of this invention is the production of novel N-(tert-butoxycarbonyl)-intermediates which may be used in the preparation of pharmaceutically active esters of .alpha.-methyl-3,4-dihydroxyphenylalanine.